SNP Wars
The NanoChip
High-Efficiency Fluorescence Polarization
The NanoChip (Back to Top)
Glen Evans, professor of internal medicine at UT Southwestern, performed a study using the NanoChip system to genotype more than 200 individuals for 12 clinically relevant SNPs. He presented evidence for 100% accuracy on all 2400 individual SNP calls. The study also identified one rare mutation, exceeding the results obtained with DNA sequencing. Eight percent of the SNP scores determined using current DNA sequencing technology were corrected by using the NanoChip system.
Moreover, the NanoChip study demonstrated its multiplexing capability and flexibility. Amplified genomic DNA from one patient was accurately scored for as many as 12 functional SNPs of pharmacogenomic significance on a single microelectronic chip, demonstrating how the NanoChip could be used for clinical diagnostic panels. In a second experimental design, 32 patient samples arrayed on a single microchip were scored for 1 SNP per sample, demonstrating the use of the NanoChip for genotyping studies.
Glen Evans, who holds the George L. MacGregor Distinguished Chair in Biomedical Sciences at UT Southwestern, stated, "Genotyping by DNA sequencing is particularly difficult for heterozygotes, which is a mixture of two variants in the same sample. The NanoChip system is especially powerful for unambiguous detection and identification of heterozygotes, as shown in our loss-of-heterozygosity studies with lung cancer genes."
NanoChip discriminates single base pair mismatch.
Nanogen plans to begin selling its NanoChip system this year. The NanoChip system uniquely uses electronically accelerated hybridization under low salt conditions, avoiding most of the problems with DNA conformation and secondary structures, whereas most sequencing and primer extension technologies require high salt conditions. The NanoChip system allows the user to array and analyze DNA on its NanoChip cartridges in user selectable formats in a single day with walk-away automation. The NanoChip system integrates advanced microelectronics and molecular biology into a platform technology with broad commercial applications in the fields of biomedical research, genomics, medical diagnostics, genetic testing, and drug discovery.
For more information: Kieran T. Gallahue, Senior Vice President/CFO, Nanogen Inc., 10398 Pacific Center Ct., San Diego, CA 92121. Tel: 858-410-4607.
High-Efficiency Fluorescence Polarization (Back to Top)
LJL presented results from two SNP genotyping studies performed at Columbia and VCU, both using LJL's High Efficiency Fluorescence Polarization (HEFP-SNP) platform. James Knowles, co-author of the Columbia data, studied a SNP in the promoter of the cholecystokinin (CCK) gene, a gene implicated in panic disorder diseases. Knowles genotyped 246 individuals in families with panic disorder. All families showed the expected inheritance patterns. Knowles said that, "the inherent simplicity of the homogeneous HEFP method combined with its cost-efficiency were the factors that first attracted our attention to LJL's platform. We achieved both impressive accuracy and a high rate of genotyping within weeks."
Richard Straub, director of the Molecular Genetics Laboratory at VCU, is using the LJL HEFP platform in the hunt for schizophrenia genes on chromosomes 5 and 6. For these linkage disequilibrium studies, novel SNPs are being generated by DNA sequencing, and then over 1400 individuals from high-density schizophrenia families are genotyped. Straub stated, "We are very pleased—the method is inexpensive, robust, capable of automation, and potentially quite high throughput. Based on confirmation of over 200 genotypes from six different SNPs by direct sequencing, we have estimated the accuracy to be about 99.5%. With a bit more effort towards optimization, we would hope that this figure will improve considerably."
LJL BioSystems supplies infrastructure tools to pharmaceutical and biotech companies engaged in the highly competitive search for new medicines in the genomics era. In August 1999, LJL launched its Genomics Science Group to further commercialize the company's technology in SNP genotyping. Since then, several leading genomics customers have adopted the LJL HEFP-SNP genotyping platform.
For more information: LJL BioSystems Inc. 404 Tasman Dr., Sunnyvale, CA 94089. Tel: 408-541-8761. Fax: 408-541-8786.